Reaction Mechanism of Mammalian Mitochondrial Cytochrome c Oxidase
Cytochrome c oxidase (COX) is the terminal oxidase of the mitochondrial respiratory system. This enzyme reduces molecular oxygen (O2) to water in a reaction coupled with the pumping of protons across the mitochondrial inner membrane. Progress in investigating the reaction mechanism of this enzyme has been limited by the resolution of its X-ray structure. Bovine heart COX has provided the highest resolution (1.8 Å) X-ray structure presently available among the terminal oxidases. The reaction mechanism of the bovine heart enzyme has been the most extensively studied, particularly with respect to (1) the reduction of O2 to water without release of reactive oxygen species, (2) the mechanism of coupling between the O2 reduction process and proton pumping, (3) the structural basis for unidirectional proton transfer (proton pumping), and (4) the effective prevention of proton leakage from the proton-pumping pathway to the proton pathway used for generation of water molecules. In this chapter, we will review recent structural studies of bovine heart COX and discuss the mechanisms described earlier in context of the structural data.
KeywordsProton Transfer Electron Equivalent Reduction Site Spin Heme Fatty Acid Tail
This work is supported in part by the Grant-in-Aid for Scientific Research 2247012 (S.Y.), the Targeted Protein Research Program, and the Global Center of Excellence Program, each provided by the Japanese Ministry of Education, Culture, Sports, Science and Technology. S.Y. is a Senior Visiting Scientist in the RIKEN Harima Institute.
- Caughey WS, Wallace WJ, Volpe JA, Yoshikawa S (1976) Cytochrome c oxidase. In: Boyer PD (ed) The enzymes, volume XIII. Oxidation-reduction, Part C, 3rd edn. Academic, New YorkGoogle Scholar
- Isaacs NS (1995) Physical organic chemistry, 2nd edn. Longman, EssexGoogle Scholar
- Konstantinov A, Siletsky S, Mitchell D, Kaulen A, Gennis RB et al (1997) The roles of the two proton input channels in cytochrome c oxidase from Rhodobacter sphaeroides probed by the effects of site-directed mutations on time-resolved electrogenic intraprotein proton transfer. Proc Natl Acad Sci USA 94:9085–9090PubMedCrossRefGoogle Scholar
- Yakushiji E, Okunuki K (1941) Isolierung der a-Komponents des Cytochroms und ihre Eigenschaften. Proc Imp Acad Jpn 17:38–40Google Scholar
- Yamashita E, Aoyama H, Yao M, Muramoto K et al (2005) Absolute configuration of the hydroxyfarnesylethyl group of haem A, determined by X-ray structural analysis of bovine heart cytochrome c oxidase using methods applicable at 2.8 Angstrom resolution. Acta Crystallogr D Biol Crystallogr D61:1373–1377CrossRefGoogle Scholar